ArticleBreast cancer research and treatment2012
Cross-platform pathway-based analysis identifies markers of response to the PARP inhibitor olaparib.
Article in Breast cancer research and treatment, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 74 citations in OpenAlex.
- Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial.Cancer cell · 2021Trial
- Altered MDC1 Interactions and Dysfunctional DNA Repair in Lobular Breast Cancer Confers Sensitivity to PARP Inhibition.Cancer research · 2026Article
- Multi-omics comprehensive analysis identified KIF22 and KRAS as highly synthetic lethal pairs for triple-negative breast cancer.Frontiers in oncology · 2026Article
- Long non-coding RNAs as a biomarker for homologous recombination deficiency and parp inhibitor sensitivity in high-grade serous ovarian cancers.Communications biology · 2025Article
- Hormone Receptor-Positive HER2-Negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple-Negative Breast Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Multi-scale characterisation of homologous recombination deficiency in breast cancer.Genome medicine · 2023Article
- Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727).Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Review
- Loss of HRD functional phenotype impedes immunotherapy and can be reversed by HDAC inhibitor in ovarian cancer.International journal of biological sciences · 2023Article
- The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy.Journal of experimental & clinical cancer research : CR · 2022Review
- Predictive biomarkers for molecularly targeted therapies and immunotherapies in breast cancer.Archives of pharmacal research · 2022Review
- Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies.Cancer cell · 2022Article
- Review
- Expanding the Use of PARP Inhibitors as Monotherapy and in Combination in Triple-Negative Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Phase 2 Study of Olaparib in Malignant Mesothelioma and Correlation of Efficacy With Germline or Somatic Mutations inJTO clinical and research reports · 2021Article
- Programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) gene expression in primary breast cancer.Breast cancer research and treatment · 2021Article
- Clinicopathological and Functional Evaluation Reveal NBS1 as a Predictor of Platinum Resistance in Epithelial Ovarian Cancers.Biomedicines · 2021Article
- Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial.Frontiers in oncology · 2021Article
- STAT3 imparts BRCAness by impairing homologous recombination repair in Epstein-Barr virus-transformed B lymphocytes.PLoS pathogens · 2020Article
- Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in DNA repair. PARP inhibitors can act as chemosensitizers, or operate on the principle of synthetic lethality when used as single agent. Clinical trials have shown drugs in this class to be promising for BRCA mutation carriers. We postulated that inability to demonstrate response in non-BRCA carriers in which BRCA is inactivated by other mechanisms or with deficiency in homologous recombination for DNA repair is due to lack of molecular markers that define a responding subpopulation. We identified candidate markers for this purpose for olaparib (AstraZeneca) by measuring inhibitory effects of nine concentrations of olaparib in 22 breast cancer cell lines and identifying features in transcriptional and genome copy number profiles that were significantly correlated with response. We emphasized in this discovery process genes involved in DNA repair. We found that the cell lines that were sensitive to olaparib had a significant lower copy number of BRCA1 compared to the resistant cell lines (p value 0.012). In addition, we discovered seven genes from DNA repair pathways whose transcriptional levels were associated with response. These included five genes (BRCA1, MRE11A, NBS1, TDG, and XPA) whose transcript levels were associated with resistance and two genes (CHEK2 and MK2) whose transcript levels were associated with sensitivity. We developed an algorithm to predict response using the seven-gene transcription levels and applied it to 1,846 invasive breast cancer samples from 8 U133A/plus 2 (Affymetrix) data sets and found that 8-21 % of patients would be predicted to be responsive to olaparib. A similar response frequency was predicted in 536 samples analyzed on an Agilent platform. Importantly, tumors predicted to respond were enriched in basal subtype tumors. Our studies support clinical evaluation of the utility of our seven-gene signature as a predictor of response to olaparib.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.